Identification of LRRC46 as a novel candidate gene for high myopia.

High myopia (HM) is the primary cause of blindness, with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these tissues. In a previously reported myopic linkage region, MYP5 (17q21-22), a potential candidate gene, LRRC46 (c.C235T, p.Q79X), was identified in a large Han Chinese pedigree. LRRC46 is expressed in various eye tissues in humans and mice, including the retina, cornea, and sclera. In subsequent cell experiments, the mutation (c.C235T) decreased the expression of LRRC46 protein in human corneal epithelial cells (HCE-T). Further investigation revealed that Lrrc46-/- mice (KO) exhibited a classical myopia phenotype. The thickness of the cornea and sclera in KO mice became thinner and more pronounced with age, the activity of limbal stem cells decreased, and microstructural changes were observed in the fibroblasts of the sclera and cornea. We performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type (WT) mice, which indicated a significant downregulation of the collagen synthesis-related pathway (extracellular matrix, ECM) in KO mice. Subsequent in vitro studies further indicated that LRRC46, a member of the important LRR protein family, primarily affected the formation of collagens. This study suggested that LRRC46 is a novel candidate gene for HM, influencing collagen protein VIII (Col8a1) formation in the eye and gradually altering the biomechanical structure of the cornea and sclera, thereby promoting the occurrence and development of HM.

Free-hand technique of C7 pedicle screw insertion using a simply defined entry point without fluoroscopic guidance for cervical spondylotic myelopathy patients with C3 to C6 instrumented by lateral mass screws: a retrospective cohort study.

BACKGROUND: Nowadays, both lateral mass screw (LMS) and pedicle screw were effective instrumentation for posterior stabilization of cervical spine. This study aims to evaluate the feasibility of a new free-hand technique of C7 pedicle screw insertion without fluoroscopic guidance for cervical spondylotic myelopathy (CSM) patients with C3 to C6 instrumented by lateral mass screws. METHODS: A total of 53 CSM patients underwent lateral mass screws instrumentation at C3 to C6 levels and pedicle screw instrumentation at C7 level were included. The preoperative 3-dimenional computed tomography (CT) reconstruction images of cervical spine were used to determine 2 different C7 pedicle screw trajectories. Trajectory A passed through the axis of the C7 pedicle while trajectory B selected the midpoint of the base of C7 superior facet as the entry point. All these 53 patients had the C7 pedicle screw inserted through trajectory B by free-hand without fluoroscopic guidance and the postoperative CT images were obtained to evaluate the accuracy of C7 pedicle screw insertion. RESULTS: Trajectory B had smaller transverse angle, smaller screw length, and smaller screw width but both similar sagittal angle and similar pedicle height when compared with trajectory A. A total of 106 pedicle screws were inserted at C7 through trajectory B and only 8 screws were displaced with the accuracy of screw placement as high as 92.5%. CONCLUSION: In CSM patients with C3 to C6 instrumented by LMS, using trajectory B for C7 pedicle screw insertion is easy to both identify the entry point and facilitate the rod insertion.

China Glaucoma Treatment Pattern Study I-Primary Angle-Closure Glaucoma: protocol for a multicentre, retrospective, observational study.

INTRODUCTION: Primary angle-closure glaucoma (PACG) is a leading cause of irreversible blindness globally, and the number of patients with PACG rises every year. Yet, there is a lack of knowledge about the clinical characteristics, therapeutic options and profile of patients with PACG in China. Hence, we design the China Glaucoma Treatment Pattern Study Ⅰ-Primary Angle-Closure Glaucoma (Ch-GTPⅠ). The objective of this paper is to describe the design and methodology of Ch-GTP. The aim of this study is to characterise the profile and trend associated with initial PACG treatment for the last 10 years in China. METHODS: Ch-GTPⅠ is a national multicentre retrospective observational study that will randomly sample from 50 hospitals throughout China. Over 7000 patient records hospitalised for initial PACG treatment from 2011 to 2020 will be selected randomly. The data from electronic medical records will be uploaded to an encrypted online platform that will receive and collate data from all collaborating hospitals. Data abstraction and monitoring will be performed in a standardised manner by trained statisticians to ensure consistency. Systematic data cleaning will also be conducted by statisticians to ensure data integrity before final data storage. The outcomes will include four broad categories: (1) demographics, (2) clinical characteristics, (3) therapeutic strategies and procedures and (4) early outcomes at discharge. The demographic characteristics and early outcomes will be summarised using descriptive statistics. Comparative analyses of characteristics and treatment pattern changing trends for different regions and years will be used to test for significant differences (t-test or Mann-Whitney U test). ETHICS AND DISSEMINATION: The collaborating hospitals obtained local approval based on a standard ethics application from internal ethics committees or acknowledged an existent ethics approval of the leading institution with approval from internal ethics committees. Due to the retrospective nature, written informed consent from patients was waived by the ethics committee. The results will be published in academic journals and presented at national and international academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2100054643.

Function and Morphology of the Meibomian Glands Using a LipiView Interferometer in Rotating Shift Medical Staff.

PURPOSE: To investigate the function and morphology of meibomian glands (MG) in night shift medical staff (MS). METHODS: Sixty-two eyes of 31 patients in the MS group and 59 eyes of 31 patients in the control group were consecutively enrolled. All participants completed Ocular Surface Disease Index (OSDI) and Standard Patient Dry Eye Evaluation (SPEED) questionnaires for dry eye severity, as well as Schirmer I and tear break-up time (TBUT) tests. LipiView® II Ocular Surface Interferometer was used for lipid layer thickness (LLT), MG dropout, and partial blink (PB) rate tests. MG expression was measured with an MG evaluator. RESULTS: The OSDI score in the MS group was 22.39 ± 13.42, which was significantly higher than that in the control group (9.87 ± 6.64 Z = -3.997, P=0.001). The SPEED score in the MS group was 7.94 ± 3.81, which was significantly higher than in the control group (3.65 ± 2.11, Z = -4.766, P=0.001). There was no significant difference in Schirmer I test between the MS group and control group (Z = -1.346, P=0.178). TBUT in MS group was significantly shorter than that in the control group (Z = -5.201, P=0.001). The mean LLT of the MS group was 55.02 ± 21.17 nm significantly thinner than that of the control group 72.76 ± 21.62 nm (Z = -4.482, P=0.001). MG loss occurred in 45.16% of affected eyes in the MS group and 16.13% of affected eyes in the control group, and the difference was statistically significant (χ 2 = 14.352, P=0.001). MG yielding liquid secretion and MG yielding secretion score were significantly lower in the MS group than in the control group (Z = -3.641, P=0.001; Z = -3.146, P=0.001, resp.). There was a negative correlation between mean LLT and SPEED score (Spearman r = -0.363, P=0.045). CONCLUSIONS: Night shift MS had a higher incidence of MGD compared to day workers.

Aggressive natural killer/T-cell lymphoma masquerading as acute orbital hemorrhage: a case report.

Natural killer T-cell lymphoma (NKTCL) is a highly aggressive tumor that usually affects the nasal cavity and/or paranasal sinuses. Primary orbital NKTCL is extremely rare, with only a few cases reported in the literature. The clinical presentation of orbital involvement by NKTCL is atypical and usually misdiagnosed as orbital cellulitis or orbital pseudotumor. A 23-year-old male patient was admitted to our hospital complaining of severe eye pain and manifested as acute orbital hemorrhage. Isolated orbital natural killer T-cell lymphoma (NKTCL) was confirmed by biopsy. This patient's orbital NKTCL did not respond to CHOP (cyclophosphamide, epirubicin, vincristine, prednisone) chemotherapy, but shrank significantly after receiving 1 cycle of C-SMILE (chidamide, steroid, methotrexate, isophosphamide, L-pegaspargase, etoposide). However, he still died after 3 cycles of C-SMILE chemotherapy at a follow-up time of 4 months. Primary orbital NKTCL can present clinically as a rare acute orbital hemorrhage, and the disease is aggressive and has a poor prognosis.

Delayed PARP-1 Inhibition Alleviates Post-stroke Inflammation in Male Versus Female Mice: Differences and Similarities.

Post-stroke inflammation is almost involved in the whole process of stroke pathogenesis, which serves as a prime target for developing new stroke therapies. Despite known sex differences in the incidence and outcome of stroke, few preclinical or clinical studies take into account sex bias in treatment. Recent evidence suggests that poly (ADP-ribose) polymerase (PARP)-1 inhibitor exerts sex-specific neuroprotection in the ischemic stroke. This study was aimed to investigate the effects of delayed PARP-1 inhibition on post-stroke inflammation and possible sexual dimorphism, and explore the possible relevant mediators. In male and female C57BL/6 mice subjected to transit middle cerebral artery occlusion (MCAO), we found that delayed treatment of PARP-1 inhibitor at 48 h following reperfusion could comparably alleviate neuro-inflammation at 72 h after stroke. Whereas, more remarkable reduction of iNOS and MMP9 induced by PARP-1 inhibition were found in male MCAO mice, and the improvement of behavioral outcomes was more prominent in male MCAO mice. In addition, we further identified that PARP-1 inhibitor might equivalently suppress microglial activation in males and females in vivo and in vitro. With proteomic analysis and western blotting assay, it was found that stroke-induced peroxiredoxin-1 (Prx1) expression was significantly affected by PARP-1 inhibition. Interestingly, injection of recombinant Prx1 into the ischemic core could block the anti-inflammatory effects of PARP-1 inhibitor in the experimental stroke. These findings suggest that PARP-1 inhibitor has effects on regulating microglial activation and post-stroke inflammation in males and females, and holds promise as a novel therapeutic agent for stroke with extended therapeutic time window. Efforts need to be made to delineate the actions of PARP-1 inhibition in stroke, and here we propose that Prx1 might be a critical mediator.

Evaluation of FGF10 as a candidate gene for high myopia in a Han Chinese population.

BACKGROUND: Fibroblast growth factor 10 (FGF10) is implicated in the growth and development of the eye. Four singles nucleotide polymorphisms (SNPs) in the FGF10 gene (including rs1384449, rs339501, rs12517396 and rs10462070) were found to be associated with extreme myopia (EM, refractive error ≤ - 10.0 diopters) in Japanese and Chinese Taiwan population. This case-control association study was conducted to explore the relationship between these four SNPs and high myopia in a western Chinese population. METHODS: A total of 869 high myopia patients (HM, including 485 EM patients) and 899 healthy controls were recruited. These four SNPs were genotyped using the ABI SNaPshot method. Five genetic models (allelic, homozygous, heterozygous, dominant, and recessive) were applied to further evaluate the possible correlation between the SNPs and high myopia. The linkage-disequilibrium block (LD) structure was tested by Haploview Software. RESULTS: In our study, no statistically significant differences were found between HM/EM patients and controls after Bonferroni multiple-correction (P > 0.05) in the allele frequencies of these four SNPs in the FGF10 gene. We further found that rs12517396AA and rs10462070GG carriers showed a decreased risk of HM/EM compared with rs12517396AC + CC and rs10462070GA + AA carriers (P = 0.045, OR = 0.366; P = 0.021, OR = 0.131; P = 0.03, OR = 0.341; P = 0.015, OR = 0.122; respectively). Additionally, rs12517396AA and rs10462070GG carriers showed the same decreased risk of HM/EM compared with rs12517396CC and rs10462070AA carriers (P = 0.048, OR = 0.370; P = 0.023, OR = 0.133; P = 0.032, OR = 0.346; P = 0.017, OR = 0.126). However, these significant associations between rs12517396/rs10462070 and HM/EM disappeared after Bonferroni multiple-correction (P > 0.05). CONCLUSION: Our findings indicate that rs12517396 and rs10462070 had marginal association with HM and EM. The other two common polymorphisms in FGF10 unlikely have significant effects in the genetic predisposition to HM/EM in western Chinese population. Further replication studies are needed to validate our findings in both animal models and human genetic epidemiologic studies.

OCT4B-190 protects against ischemic stroke by modulating GSK-3ß/HDAC6.

OCT4 is a key regulator in maintaining the pluripotency and self-renewal of embryonic stem cells (ESCs). Human OCT4 gene has three mRNA isoforms, termed OCT4A, OCT4B and OCT4B1. The 190-amino-acid protein isoform (OCT4B-190) is one of the major products of OCT4B mRNA, the biological function of which is still not well defined. Recent evidence suggests that OCT4B-190 may function in the cellular stress response. The glycogen synthase kinase-3ß (GSK-3ß) and histone deacetylase 6 (HDAC6) are also key stress modulators that play critical roles in the ischemic cascades of stroke. Hence, we here further investigated the effects of OCT4B-190 in the experimental stroke, and explored the underlying roles of GSK-3ß and HDAC6. We found that OCT4B-190 overexpression enhanced neuronal viability at 24 h after oxygen-glucose deprivation (OGD) treatment. Moreover, in male C57BL/6 mice subjected to transit middle cerebral artery occlusion (MCAO), OCT4B-190 overexpression reduced infarct volume and improved neurological function after stroke. Notably, we found spatio-temporal alterations of GSK-3ß and HDAC6 in the ischemic cortex and striatum, which were affected by adenovirus-mediated OCT4B-190 overexpression. OCT4B-190 demonstrated similar impacts on neuronal cultures in vitro, downregulating OGD-induced GSK-3ß activity and HDAC6 expression. In addition, we found that GSK-3ß and HDAC6 were co-expressed in the cytoplasm of neurons, and OCT4B-190 had an effect on interactions between GSK-3ß and HDAC6 in neuronal cultures subjected to OGD treatment. These findings suggest that OCT4B-190 exerts neuroprotection in the experimental stroke potentially by regulating actions of GSK-3ß and HDAC6 simultaneously, which may be an attractive therapeutic strategy for ischemic stroke.

Downregulation of the expression of the lncRNA MIAT inhibits melanoma migration and invasion through the PI3K/AKT signaling pathway.

BACKGROUND: Long noncoding RNA MIAT expression is related to the development of some diseases. However, the role of MIAT in melanoma was has seldom been studied. OBJECTIVE: To investigate the effect of the lncRNA MIAT on melanoma cells. METHOD: Microarray was used to analyze the lncRNAs expression in tissue samples. The expression of the lncRNA MIAT was detected by qRT-PCR. A CCK-8 assay was used to assess cell viability, and cell counting was used to analyze cell proliferation. Wound healing and Transwell invasion assays were used to detect the migration and invasion abilities, respectively, of melanoma cells. Western blotting was performed to explore the molecular mechanisms of MIAT in melanoma. RESULTS: The lncRNA MIAT was overexpressed in melanoma. The overexpression of MIAT promoted cell proliferation, cell invasion and migration, while the knockdown of MIAT expression got the opposite results. MIAT significantly upregulated the phosphorylation of PI3K and AKT and promoted cMyc and cyclin D1 protein expression. CONCLUSION: LncRNA MIAT was a key factor to promote cell invasion, migration and proliferation through the PI3K/AKT signaling pathway. These findings may give us a potential way to treat melanoma.

Inhibition of microRNA-129-5p expression ameliorates ultraviolet ray-induced corneal epithelial cell injury via upregulation of EGFR.

Existing evidence has highlighted the effect of ultraviolet light radiation leading to corneal epithelium impairment. During this study, we aim to investigate the effect of microRNA-129-5p (miR-129-5p) on the wound healing process of corneal epithelial cells (CECs) induced by ultraviolet rays in mice by targeting epidermal growth factor receptor (EGFR). First, mouse models of ultraviolet ray-induced CEC injury were established and intrastromally injected with different mimic, inhibitor, and short interfering RNA (siRNA) to detect the effect of miR-129-5p on CEC injury. Subsequently, the corneal tissues were obtained to detect the antioxidant ability and EGFR-positive expression rate. The dual-luciferase reporter gene assay was used to test whether EGFR could directly target miR-129-5p. To further investigate the specific mechanism of miR-129-5p and EGFR in CEC injury, CECs were cultured and transfected with miR-129-5p mimic, miR-129-5p inhibitor, siRNA-EGFR, and miR-129-5p inhibitor + siRNA-EGFR. miR-129-5p has been proven to directly target EGFR. Inhibition of miR-129-5p is able to increase the antioxidant capacity, EGFR-positive rate and the expressions of EGFR, B-cell lymphoma-2, zonula occluden-1, occludin, and keratinocyte growth factor-2, but decrease the expression of vascular endothelial growth factor, BCL2-associated X protein, interleukin (IL)-1ß, and IL-4. Inhibition of miR-129-5p arrests cells at the S and G2 phases and decreases apoptosis. Our study provides evidence stating that inhibiting miR-129-5p and upregulating EGFR could aid in the repair of mice CEC injury induced by ultraviolet radiation. Therefore, inhibition of miR-129-5p might provide a basic theory in the repair of CEC injury caused by ultraviolet rays.

[Polydatin ameliorates myocardial fibrosis in rats by up-regulating SIRT3 and SDF-1].

Objective To investigate the effects and the possible mechanisms of polydatin on the myocardial fibrosis and cytokines of myocardium induced by adriamycin. Methods Twenty male SD rats was divided into four groups, 5 rats in every group. Control group (only fed with conventional diet), adriamycin group (treated with intraperitoneal injection of 2.5 mg/kg adriamycin for twice a week), polydatin treatment group (treated with intraperitoneal injection of 50 mg/kg polydatin for once a day) and nicotinamide treatment group (treated with intraperitoneal injection of 500 mg/kg SIRT3 inhibitor nicotinamide for twice a week). The effects of polydatin on adriamycin induced myocardial fibrosis and collagen expression in myocardium were evaluated by immunohistochemistry. The content of hydroxyproline (HYP) in myocardium was detected by enzyme labeling method. Spectrofluorometry was used to determine the level of superoxide dismutase (SOD) activity, glutathione (GSH) and malonaldehyde (MDA) level. ELISA was used to detect the content of tumor necrosis factor α(TNF-α), interleukin 1(IL-1)and IL-10. The levels of SIRT1, SIRT3, transforming growth factor-ß (TGF-ß) and stromal cell-derived factor-1(SDF-1) were examined by real-time quantitative PCR and Western blotting.Results Treatment with adriamycin promoted the myocardial fibrosis, reduced the level of IL-10, increased the level of TNF-α, IL-1 in myocardial tissue. The mRNA and protein levels of SIRT3 and SDF-1 was inhibited by adriamycin, whereas the expression of TGF-ß was promoted. The results showed that polydatin inhibited the fibrosis of myocardium induced by adriamycin, decreased the level of HYP, collagen III and MDA , whereas the level of SOD and GSH was increased. Treatment with nicotinamide attenuated the inhibitory effects of polydatin on the fibrosis of myocardium, inhibited the expression of SIRT3 and SDF-1, promoted the expression of TGF-ß. Conclusion Polydatin upregulates the expression of SIRT3 to increase the ability of anti-fibrosis and reduce the level of oxidative stress induced by adriamycin, inhibits the relase of cytokines.

Exome sequencing study of 20 patients with high myopia.

BACKGROUND: High myopia is a common ocular disease worldwide. To expand our current understanding of the genetic basis of high myopia, we carried out a whole exome sequencing (WES) study to identify potential causal gene mutations. METHODS: A total of 20 individuals with high myopia were exome sequenced. A novel filtering strategy combining phenotypes and functional impact of variants was applied to identify candidate genes by multi-step bioinformatics analyses. Network and enrichment analysis were employed to examine the biological pathways involved in the candidate genes. RESULTS: In 16 out of 20 patients, we identified 20 potential pathogenic gene variants for high myopia. A total of 18 variants were located in myopia-associated chromosomal regions. In addition to the novel mutations found in five known myopia genes (ADAMTS18, CSMD1, P3H2, RPGR, and SLC39A5), we also identified pathogenic variants in seven ocular disease genes (ABCA4, CEP290, HSPG2, PCDH15, SAG, SEMA4A, and USH2A) as novel candidate genes. The biological processes associated with vision were significantly enriched in our candidate genes, including visual perception, photoreceptor cell maintenance, retinoid metabolic process, and cellular response to zinc ion starvation. DISCUSSION: Systematic mutation analysis of candidate genes was performed using WES data, functional interaction (FI) network, Gene Ontology and pathway enrichment. FI network analysis revealed important network modules and regulator linker genes (EP300, CTNNB1) potentially related to high myopia development. Our study expanded the list of candidate genes associated with high myopia, which increased the genetic screening performance and provided implications for future studies on the molecular genetics of myopia.

Macular integrity assessment to determine the association between macular microstructure and functional parameters in diabetic macular edema.

AIM: To respectively evaluate macular morphological features and functional parameters by using spectral-domain optical coherence tomography (SD-OCT) and macular integrity assessment (MAIA) in patients with diabetic macular edema (DME). METHODS: This prospective, non-controlled, open study included 61 eyes of 38 consecutive patients with DME. All patients underwent best-corrected visual acuity (BCVA) measurement, MAIA microperimetry, and SD-OCT. DME morphology, including central retinal thickness (CRT) and central retinal volume (CRV); integrity of the external limiting membrane (ELM) and photoreceptor inner segment/outer segment (IS/OS) junction; and the deposition of hard macular exudates were assessed within a 1000-µm central subfield area. MAIA microperimetry parameters evaluated were average threshold (AT)-retinal sensitivity, macular integrity index (MI), fixation points within a circle of radius 1° (P1) and 2° (P2), and bivariate contour ellipse area considering 63% and 95% of the fixation points (A63 and A95, respectively). RESULTS: MI was significantly higher in eyes with disrupted ELM or IS/OS, compared with eyes with intact ELM and IS/OS. Values of BCVA (logMAR), total AT, AT within 1000-µm diameter, P2, A63, A95, and CRT were significantly worse in eyes with disrupted IS/OS, compared with eyes with intact IS/OS. The values of BCVA (logMAR), AT within 1000-µm diameter, and CRT were significantly worse in eyes with disrupted ELM, compared with eyes with intact ELM. These parameters were not significantly different between eyes with or without hard macular exudate deposition. CRV was not significantly different in the presence or absence of the integrity of ELM, IS/OS, or deposition of hard macular exudates. At the center, nasal and temporal sectors of the fovea, significant negative correlations were observed between retinal thickness and AT of the corresponding area. At the inferior and superior sectors of the fovea, no correlations were observed between retinal thickness and AT of the corresponding area. In the intact IS/OS group, significant negative correlations were observed between CRT and central AT. There was no correlation between retinal sensitivity and thickness when the IS/OS layer was disrupted. Multiple linear regression analyses revealed that IS/OS integrity was an independent factor affecting MI. CONCLUSION: Functional (BCVA and visual field) and morphological parameters (retinal thickness) were significantly associated with an intact IS/OS. Local photoreceptor integrity was a strong predictor of local visual function throughout the retina. MI revealed the functional status in DME, reflecting the IS/OS juction status in the macula.

Mesenchymal marker and LGR5 expression levels in circulating tumor cells correlate with colorectal cancer prognosis.

PURPOSE: The presence of circulating tumor cells (CTCs) has been found to correlate with colorectal cancer (CRC) prognosis, whereas epithelial-mesenchymal transition (EMT) in CTCs has been found to be associated with CRC metastasis. LGR5 is a known target of Wnt signaling and plays an important role in CRC development. The aim of this study was to assess the clinical relevance of EMT and LGR5 expression in CTCs from CRC patients. METHODS: Sixty-six CRC patients were included in this study. The detection and expression of EMT phenotypes in CTCs from these patients were assessed using CanPatrol™ CTC enrichment and mRNA in situ hybridization (ISH), respectively. LGR5 expression in the CTCs was assessed using mRNA ISH. RESULTS: CTCs were detected in 86.4% (57/66) of the CRC patients included. Both the numbers of total CTCs and of CTCs displaying a mesenchymal phenotype (M+ CTCs) were found to significantly correlate with advanced disease stages and the occurrence of metastasis (p < 0.05). An adjusted multivariate analysis also indicated that the number of M+ CTCs significantly correlated with the occurrence of metastasis (p = 0.031). Additionally, we found that a high LGR5 expression level significantly correlated with the occurrence of metastasis (p < 0.05). We also found that the presence of ≥ 6 CTCs or ≥ 3 M+ CTCs per 5 ml blood significantly correlated with disease progression (p < 0.05). Patients with ≥ 6 CTCs or ≥ 3 M+ CTCs per 5 ml blood were found to exhibit poorer progression-free survival (PFS) and overall survival (OS) rates (p < 0.05 in all cases). Using Cox regression analyses, we found that only total CTC numbers remained as independent prognostic factors for a worse PFS (p = 0.043). CONCLUSIONS: From our data we conclude that CTC numbers and EMT phenotypes may serve as prognostic markers for disease progression and metastasis in CRC patients. In addition, we conclude that LGR5 expression in CTCs may serve as a marker for CRC metastasis.

Protective effect of resveratrol against light-induced retinal degeneration in aged SAMP8 mice.

PURPOSE: The purpose of this study was to determine the protective effects of Resveratrol (RESV) on acute bright light-induced retinal degeneration in aged senescence accelerated mouse strain. METHODS: Ten three-month-old male SAMP8 mice (prone to aging) were randomly assigned to two experimental dietary groups: one untreated group and one RESV treatment group (n=20 eyes for each group). After 30 days of treatment, mice were exposed to intense bright light. Ten male SAMR1 mice (resistant to aging) served as control (n=20 eyes). The protective effects of RESV administration on light-induced retinal degeneration in SAMP8 strain as well as the effect of bright light damage in the retinas of SAMP8 mice were analyzed by electroretinography (ERG), retinal histology, mRNA, protein and lipid profile. RESULTS: 68%-85% of a-wave amplitude and 72%-92% of b-wave amplitude were persevered by RESV in SAMP8 mice that were exposed to light damage. Also, RESV preserved their photoreceptor nuclei. mRNA expression of neuroprotective factors leukemia inhibitory factor (LIF), brain derived neurotrophic factor (BDNF), oncostatin M (OSM), cardiotrophin 1(CT-1) and cardiotrophin-like cytokine (CLC) were up-regulated 28, 8, 7, 5 and 9-fold in SAMP8 mice after RESV treatment. In addition, RESV could suppress the NF-κB pathway by down-regulating the expression of pIκB. Light damage led to increase of saturated FA, monoenoic FA, n6 PUFA and n6/n3 ratio and decrease of Docosahexaenoic acid (DHA). There was no significant difference on DHA and the ratio of n6/n3-FA between the untreated and RESV treated SAMP8 mice. CONCLUSIONS: Collectively, our study provides evidence that RESV prevents light-induced retinal damage associated with aging.

Evaluation of genome-wide susceptibility loci for high myopia in a Han Chinese population.

PURPOSE: High myopia (HM) is a common cause of visual impairment worldwide. Previous genome-wide association studies have reported that seven single nucleotide polymorphisms (SNPs), including rs1254319, rs3138144, rs12205363, rs17648524, rs7829127, rs1656404, and rs7084402, are associated with HM in Caucasians. The aim of this study was to investigate the association of these SNPs in Han Chinese. METHODS: SNPs were genotyped by SNaPshot method in a Chinese cohort composed of 830 HM patients and 1140 controls. RESULTS: Rs17648524 (C/G) and rs7084402 (A/G) were significantly associated with HM (p = 3.0 × 10-3, OR = 0.43; p = 3.7 × 10-2, OR = 1.25, respectively). The association of rs17648524 was also observed under the heterozygous model (CG vs. GG, p = 7.0 × 10-3, OR = 0.43) and the dominant model (CC + CG vs. GG, p = 4.0 × 10-3, OR = 0.42). The association of rs7084402 was found under the homozygous model (GG vs. AA, p = 4.0 × 10-2, OR = 1.56) and the dominant model (GG+ AG vs. AA, p = 3.8 × 10-2, OR = 1.41). Another SNP, rs7829127 (A/G), was found to be significantly associated with HM under the heterozygous model (AG vs. AA, p = 4.6 × 10-2, OR = 0.67). Furthermore, the associations of rs17648524 and rs7084402 with HM were gender-specific, with significance observed only in females but not in males. As for the other four SNPs, no associations were detected under these genetic models. CONCLUSIONS: Our findings suggested rs17648524 (intronic RBFOX1 gene) and rs7084402 (7.5kb 5' of the BICC1 gene) showed gender-specific associations with high myopia in the Han Chinese.

A Novel CRYBB2 Stopgain Mutation Causing Congenital Autosomal Dominant Cataract in a Chinese Family.

Congenital cataract is the most common cause of the visual disability and blindness in childhood. This study aimed to identify gene mutations responsible for autosomal dominant congenital cataract (ADCC) in a Chinese family using next-generation sequencing technology. This family included eight unaffected and five affected individuals. After complete ophthalmic examinations, the blood samples of the proband and two available family members were collected. Then the whole exome sequencing was performed on the proband and Sanger sequencing was applied to validate the causal mutation in the two family members and control samples. After the whole exome sequencing data were filtered through a series of existing variation databases, a heterozygous mutation c.499T

Effects of dexamethasone and HA1077 on actin cytoskeleton and ß-catenin in cultured human trabecular meshwork cells.

AIM: To investigate the effects of dexamethasone (DEX) and 1-(5-isoquinolinesulfonyl)-homopiperazine (HA1077) on actin cytoskeleton and ß-catenin in cultured human trabecular meshwork (HTM) cells. METHODS: The HTM cells were separated from human eyeball and cultured in vitro. They were divided into control group, DEX (1×10-6 mol/L) group, HA1077 (3×10-5 mol/L) group, and DEX (1×10-6 mol/L) and HA1077 (3×10-5 mol/L) group. Actin cytoskeleton and ß-catenin in HTM cells of the four groups were examined by immunofluorescence and Western blot analyses. RESULTS: In DEX group, there were reorganization of actin cytoskeleton and formation of cross linked actin networks (CLANs), which were partially reversed in DEX and HA1077 group. DEX treatment also induced an increased expression of ß-catenin, which was obviously reduced in DEX and HA1077 group. Meanwhile, the cultured HTM cells in HA1077 group had lower expression of ß-catenin than that in the control group. CONCLUSION: Our results show that HA1077 can reverse the changes of actin organization and expression of ß-catenin induced by DEX in cultured HTM cells, suggesting that HA1077 may play an important role in increasing outflow and reducing intraocular pressure.

Malibatol A enhances alternative activation of microglia by inhibiting phosphorylation of Mammalian Ste20-like kinase1 in OGD-BV-2 cells.

OBJECTIVE: To investigate the polarization effect of Malibatol A on oxygen-glucose deprivation (OGD)-BV-2 cells, and the possible molecular mechanism involved in c-Abl-MST signaling pathway. METHOD: The OGD BV-2 cell model was established. BV-2 cells were exposed to OGD for 8 h followed by reperfusion for 15 h with Malibatol A at different concentration of 0.5, 1, 2, 4, 8, 16 µM or without it. And then cells, mRNA and protein were harvested respectively. The cell viability and apoptosis were measured by MTT assay and flow cytometry. The mRNA of classical activated microglia (M1) markers (MCP-1, IL-1 and TNF-α) and alternatively activated microglia (M2) markers (Ym-1, CD206, IL-10, TGF-ß) in BV-2 cells were measured by RT-PCR. Meanwhile, the proteins of Ym-1 and CD206 was assayed by flow cytometry. Furthermore, the expression of c-Abl and MST was measured by Western blot. RESULT: Malibatol A significantly decreased apoptosis and increased viability of OGD BV-2 cells in a dose-dependent manner. In the presence of Malibatol A, the mRNA levels of Ym-1, CD206, IL-10 and TGF-ß mRNA was significantly increased in OGD-BV-2 cells, while the mRNA levels of MCP-1, IL-1 and TNF-α was obviously down-regulated. Meanwhile, the proteins of Ym-1 and CD206 was raised in OGD BV-2 cells with Malibatol A. Besides, Malibatol A also inhibited OGD-induced p-MST1(Y433) in BV-2 cells. CONCLUSION: Malibatol A could attenuate OGD-induced BV-2 cell injury and promote M2 microglia polarization. The mechanism may be related to inhibition of MST1 phosphorylation at Y433.